Triethylamine → 1-(Cyclopropylmethyl)-3-(4-(4-(4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl)-2-Propylbenzyl)piperazine-1-carbonyl)phenyl)urea

Participants

Reaction Conditions

Reaction Steps

1,1,1,3,3,3-Hexafluoro-2-(4-(hydroxymethyl)-3-propylphenyl)propan-2-ol (0.509 mmol, 161 mg) was dissolved in dichloromethane (4 mL) and triethylamine (1.527 mmol, 155 mg) was added. The mixture was cooled to 0° C. before the addition of methanesulfonyl chloride (0.611 mmol, 70.0 mg). The mixture was stirred at 0° C. for 1 hour before warming to room temperature and stirring for 1 hour. The reaction mixture was diluted with dichloromethane (50 mL) and washed with water (2×10 mL). The organic phase was dried over magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in acetonitrile (4 mL) and 1-(cyclopropylmethyl)-3-(4-(piperazine-1-carbonyl)phenyl)urea (0.510 mmol, 154 mg) was added followed by potassium carbonate (1.529 mmol, 211 mg). The mixture was heated to reflux for 16 hours. The mixture was cooled, diluted with dichloromethane (50 mL) and washed with water (2×20 mL). The organic phase was dried over magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by HPLC and treated with strong cation exchange column chromatography to afford the title compound (63 mg). MS (ESI) m/z 601.3 [M+H]+

Provenance & Evidence